Evaluation of cytogenetic complexity could improve prognosis and predict therapy response for the cancer disease chronic lymphocytic leukemia. This is shown by IGP researcher Panagiotis Baliakas, together with an international research team, in a recently published article in the journal Blood.

Chronic lymphocytic leukemia (CLL) is a cancer disease where white blood cells grow in an uncontrolled way. The disease has a very varying course and some patients deteriorate rapidly, despite treatment, whereas others can live for a long time without any therapy needed.

To improve doctors’ possibilities to give prognosis and predict when treatment will be required, researchers have for many years studied genetic aberrations associated with disease development. Recent evidence suggests that cytogenetic complexity, i.e. complex karyotype where chromosomes have abnormalities that can be observed in a microscope, could be used as a new predictive marker for prognosis and therapy response.

In the present study the researchers show that the presence of complex karyotype had an effect but that it could not be axiomatically considered unfavourable. The extent of the complex karyotype and the combination with other genetic changes were also important.

“By definition, complex karyotype is present when there are at least three structural or numeral aberrations on the chromosomes. We found that patients with five or more changes had a shorter overall survival than those with three or four, independently on other factors,” says Panagiotis Baliakas.

In contrast, patients with a low or intermediate complex karyotype, i.e. three or four chromosome aberrations, showed a poorer prognosis only if it was combined with certain other genetic changes, such as mutations in the TP53 gene.

“However, the presence of a complex karyotype is not always adverse. We also found the opposite, where patients with complex karyotype in combination with specific numerical aberrations, namely extra copies of chromosomes 12 and 19, had an extremely indolent disease course,” says Panagiotis Baliakas.

Based on the new findings the researchers propose a new hierarchical model that is capable of identifying subgroups of patients with markedly distinct clinical outcomes. In the long term, after further clinical validation, they hope that analysis of complex karyotype can be used by doctors to give prognosis and predict disease course for CLL patients.

The study was performed within the European Research Initiative on CLL (ERIC) coordinated by Panagiotis Baliakas and Kostas Stamatopoulos, Center for Research and Technology Hellas, Greece.